Influenza virus represents a major worldwide health problem as well as a potential agent for use in bioterrorism. Of the 3 known strains, influenza A is probably the best studied as it infects not only humans but other mammals and can be adapted to animal models. The major antigenic targets-hemagglutinin and neuraminidase- undergo structural changes such that antibodies formed against one strain generally are not protective with a related strain. Because of this "antigenic variation", neutralizing antibodies are not long lasting and necessitate annual vaccination. A cytotoxic T cell response to inner core proteins such as the nucleocapsid that are more conserved;or a antibody that targets conserved regions of the outer coat proteins would be desirable targets for generation of long lasting memory responses. The overall goal of this project is to investigate the cellular and molecular mechanisms underlying the role for innate immunity (complement system and natural IgM) in development of influenza-specific effector and memory T and B cells. Three specific aims are proposed: (i) Examine the role of complement C3 in the activation and expansion of influenza-specific effector and memory CDS T cells. (ii) Examine the role of complement C3 in the development of memory B cells, (iii) Examine the role of natural IgM in host innate and adaptive response to influenza.